Tat(47-57) is the 11-amino acid basic region of HIV Tat protein (human immunodeficiency virus transactivator of transcription protein, residues 47-57) which interacts with the transactivator response element (TAR) RNA, and is responsible for cell penetration. The Tat-TAR interaction is crucial for HIV proliferation, whereas the cell penetration capability of Tat is important for inducing viral proliferation in infected neighboring cells and inducing apoptosis of nearby healthy immune cells. Since the six Arg residues in this short basic region of Tat are critical for both TAR RNA recognition and cell penetration, Tat(47-57) would be an attractive system to simultaneously study the effect of Arg side chain length on two distinct bioactivities.
For example, U.S. Pat. No. 7,056,656 disclosed a Tat derived oligourea which competes with the Tat molecule of the TAR RNA in HIV-1 for the specificity to inhibit protein-nucleic acid interactions.
U.S. Patent Application No. US2009/0047272 A1 disclosed an antiviral composition, comprising a nuclease covalently attached to a target ligand (Tb)r to the inhibit the viral function by cleaving viral nucleic acids, wherein the target ligand (Tb)r may be a membrane permeating peptide comprising Arg/Lys-rich peptide, which may be selected from a peptide of YGRKKRPQRRR (SEQ ID NO: 20, HIV TAT47-57).
However, above-mentioned prior arts failed to regulate both biological activity of Tat peptide-TAR RNA recognition and cellular uptake activity, resulting in a Tat peptide having a high affinity for RNAs but probably losing its uptake ability, and vice versa. Thus, Tat(47-57) related drugs, which can effectively inhibit the replication of RNA virus (e.g. HIV virus), have not been found yet in the market.